The proposed work is designed to further examine in depth the role of hormones with emphasis on glucagon and insulin in the control of energy balance in the fetus, newborn and child. Animal models such as the sheep, rabbit, guinea pig and rat will be used for fetal studies. The normal ontogenesis of glucagon and insulin receptors on liver plasma membranes, erythrocytes (and/or moncytes) will be studied in these animals, as will the influence of hypothyroidism, glucocorticoid treatment and maternal diabetes. The role of insulin receptors in normal and abnormal carbohydrate metabolism of children will be investigated using circulating cells. The pregnant sheep with chronic indwelling catheters will be used to define glucose production, utilization and placental transfer simultaneously in mother and fetus using dual isotopic glucose infusions to mother and fetus and kinetic analysis; the effect of insulin, with and without glucose, glucagon, and catecholamines infulsed directly to the fetus or mother on these parameters will be investigated. This model can thereby be used to simulate conditions such as nesidionlastosis or maternal diabetes in humans.